No evidence for a different magnitude of the time factor for continuously fractionated irradiation and protocols including gaps in two human squamous cell carcinoma in nude mice

Abstract

Background and purpose: To study whether the magnitude of the time factor is different for continuously fractionated irradiation and for fractionation protocols including gaps. Materials and methods: Two human head and neck squamous cell carcinomas (SCCs), FaDu and GL, were transplanted subcutaneously into the right hindleg of NMRI (nu/nu) mice and irradiated with 30 fractions under ambient conditions within 2, 6 and 10 weeks. Irradiations within 6 and 10 weeks were given either as a continuous course or with a mid-course gap of 3 weeks. The end-point of the experiments was local tumor control at day 120 (FaDu) or day 180 (GL) after the end of treatment. Results: In FaDu tumors, two experimental cohorts (A, B) yielded significantly different results and were analyzed separately. In cohort A, the tumor control dose 50% ( TCD 50) increased from 37 to 89 Gy when the treatment time of continuous fractionated irradiation was extended from 2 to 10 weeks. The recovered dose/day ( D r) was 0.98 Gy (95% confidence interval, 0.72; 1.27). In cohort B, the TCD 50 increased from 35 to 63 Gy, and the D r was 0.51 Gy (0.24; 0.75). In GL tumors, the TCD 50 for continuously fractionated irradiation increased from 41 to 48 Gy. This increase was not significant, and the D r was 0.15 Gy (0; 0.30). None of the TCD 50 and D r values obtained in both tumor models for continuous irradiation vs. irradiation with a gap were significantly different. Conclusions: Prolongation of the overall treatment time of fractionated irradiation resulted in a pronounced decrease of local control in human FaDu SCC and little decrease of local control in human GL SCC. No evidence was found that the magnitude of the time factor in these tumors is different for continuous fractionation or fractionation protocols including gaps.